Network pharmacology integrated with experimental verification reveals the antipyretic characteristics and mechanism of Zi Xue powder.

CONTEXT: Zi Xue Powder (ZXP) is a traditional formula for the treatment of fever. However, the potential mechanism of action of ZXP remains unknown. OBJECTIVE: This study elucidates the antipyretic characteristics of ZXP and the mechanism by which ZXP alleviates fever. MATERIALS AND METHODS: The key targets and underlying fever-reducing mechanisms of ZXP were predicted using network pharmacology and molecular docking. The targets of ZXP anti-fever active ingredient were obtained by searching TCMSP, STITCH and HERB. Moreover, male Sprague-Dawley rats were randomly divided into four groups: control, lipopolysaccharide (LPS), ZXP (0.54, 1.08, 2.16 g/kg), and positive control (acetaminophen, 0.045 g/kg); the fever model was established by intraperitoneal LPS injection. After the fever model was established at 0.5 h, the rats were administered treatment by gavage, and the anal temperature changes of each group were observed over 10 h after treatment. After 10 h, ELISA and Western blot analysis were used to further investigate the mechanism of ZXP. RESULTS: Network pharmacology analysis showed that MAPK was a crucial pathway through which ZXP suppresses fever. The results showed that ZXP (2.16 g/kg) decreased PGE2, CRH, TNF-a, IL-6, and IL-1ß levels while increasing AVP level compared to the LPS group. Furthermore, the intervention of ZXP inhibited the activation of MAPK pathway in LPS-induced fever rats. CONCLUSIONS: This study provides new insights into the mechanism by which ZXP reduces fever and provides important information and new research ideas for the discovery of antipyretic compounds from traditional Chinese medicine.

Antioxidant properties of date seeds extract (Phoenix dactylifera L.) in alloxan induced damage in rats.

The study was conducted to examine the antioxidant activity and evaluate the protective effects of the date seeds powder kentichi against alloxan-induced damage in the liver, kidney, and pancreas in diabetic's rats. Group 1: control group, that did not receive any treatment, Group 2: alloxan was injected intraperitoneally (120 mg/kg body weight) for two days (Diab), Group 3: treated only by date seeds powder added in the diet (300 g/kg) for 6 weeks (DSPK), Group 4: alloxan-diabetic rats treated with date seeds powder (300 g/kg) (DSPK + Diab). Estimations of biochemical parameters in blood were determined. TBARS, SOD, CAT, and GPx activities were determined. A histopathological study was done by immersing pieces of both organs in a fixative solution followed by paraffin hematoxylin-eosin staining. In addition, the antioxidant activities of DSPK were evaluated by DPPH radical scavenging activity, reducing power, and ABTS free radical scavenging. The results revealed that date seeds significantly decreased serum levels of glucose, cholesterol, triglycerides, urea, creatinine, T-protein, ALP, D-bili and T-bili levels. In addition, superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) activities that had been reduced in liver, kidney, and pancreas of the treated group were restored by DSPK treatments and, therefore, the lipid peroxidation level was reduced in the liver, kidney and pancreas tissue compared to the control group. Additionally, the histological structure in these organs was restored after treatment with date seeds powder.

Jing-Fang powder ethyl acetate extracts attenuate atopic dermatitis by modulating T-cell activity.

Jing-Fang powder ethyl acetate extract (JFEE) and its isolated C (JFEE-C) possess favorable anti-inflammatory and anti-allergic properties; however, their inhibitory effects on T cell activity remain unknown. In vitro, Jurkat T cells and primary mouse CD4+ T cells were used to explore the regulatory effects of JFEE and JFEE-C as well as their potential mechanisms on activated T cells. Furthermore, T cell-mediated atopic dermatitis (AD) mouse model was established to confirm these inhibitory effects in vivo. The results showed that JFEE and JFEE-C inhibited T cell activation by suppressing the production of interleukin-2 (IL-2) and interferon-gamma (IFN-γ) without showing cytotoxicity. Flow cytometry showed the inhibitory effects of JFEE and JFEE-C on the activation-induced proliferation and apoptosis of T cells. Pretreatment with JFEE and JFEE-C also decreased the expression levels of several surface molecules, including CD69, CD25, and CD40L. Moreover, it was confirmed that JFEE and JFEE-C inhibited T cell activation by downregulating the TGF-ß-activated kinase 1 (TAK1)/nuclear kappa-light-chain-enhancer of activated B cells (NF-κB)/mitogen-activated protein kinase (MAPK) signaling pathways. The combination of these extracts with C25-140 intensified the inhibitory effects on IL-2 production and p65 phosphorylation. The oral administration of JFEE and JFEE-C notably weakened AD manifestations, including the infiltration of mast cells and CD4+ cells, epidermis and dermis thicknesses, serum levels of immunoglobulin E (IgE) and thymic stromal lymphopoietin (TSLP), and gene expression levels of T helper (Th) cells-related cytokines in vivo. The underlying mechanisms of the inhibitory effects of JFEE and JFEE-C on AD were related to attenuating T cell activity through NF-κB/MAPK pathways. In conclusion, this study suggested that JFEE and JFEE-C exhibited anti-atopic efficacy by attenuating T cell activity and might possess a curative potential for T cell-mediated diseases.

Promising effect of Geranium robertianum L. leaves and Aloe vera gel powder on Aspirin®-induced gastric ulcers in Wistar rats: anxiolytic behavioural effect, antioxidant activity, and protective pathways.

BACKGROUND: Many drugs have been restricted in the treatment of gastric ulcers (GU). So, herbal medicines are now in great demand for their better cultural acceptability, compatibility, and minimal side effects. Therefore, our study aimed to assess the protective efficacy of Aloe vera gel and Geranium robertianum extracts against Aspirin®-induced GU in Wistar rats. METHODS: Antioxidant activity and chemical composition of both herbs were analysed. Then, we divided forty female Wistar rats into five groups: a negative control group, a positive control group of Aspirin®-induced GU, and pretreated groups with Aloe Vera, geranium, and Famotidine (reference drug). The locomotor disability, anxiety-like behaviour, and ultrasonography were assessed. Ultimately, scarification of animals to determine gastric juice pH and ulcer index. Then the collection of stomach and liver for histopathological and immunohistochemical examinations, besides tracing the oxidative stress biomarkers and related genes. RESULTS: High content of polyphenols was revealed in both extracts. The pretreatment with Aloe vera gel and geranium showed significant antioxidant activities with free radical scavenging and ferric-reducing power (FRAP). Moreover, they improved the stomach architecture and alleviated anxiety-like behaviour and motor deficits. They significantly reduced the expression of proinflammatory cytokine (TNF-α), inflammatory, and oxidative stress genes (NF-KB, HO-1, Nrf-2) while increasing the Keap-1 in gastric mucosa. CONCLUSION: Data presented a significant protective effect of Aloe vera gel and geranium against Aspirin®-induced GU; they reduced gastric mucosal injury with potential anxiolytic effects through their anti-inflammatory and antioxidant properties. Therefore, they may be considered promising agents for preventing or treating gastric ulceration.

Yiyi Fuzi Baijiang Powder Alleviates Dextran Sulfate Sodium-Induced Ulcerative Colitis in Rats via Inhibiting the TLR4/NF-κB/NLRP3 Inflammasome Signaling Pathway to Repair the Intestinal Epithelial Barrier, and Modulating Intestinal Microbiota.

Ulcerative colitis (UC) is a chronic non-specific inflammatory disease of the intestine, which is prone to recurrence and difficult to cure. Yiyi Fuzi Baijiang powder (YFBP), as a classic Chinese herbal formula, is commonly used in the clinical treatment of UC. However, its potential mechanism remains unclear. In this study, we investigated the mechanism by which YFBP exerts a therapeutic effect against UC. Firstly, we used network pharmacology to screen the active ingredients and potential targets of YFBP and constructed a "drug-ingredient-target" network. Based on bioinformatics, we searched for differentially expressed genes (DEGs) associated with UC and obtained common targets. The core targets of YFBP in the treatment of UC were identified using a protein-protein interaction (PPI) network, and molecular docking techniques were used to evaluate the binding energies of the core targets and corresponding ingredients. Enrichment analysis by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) revealed that YFBP exerted therapeutic effects by regulating multiple inflammatory pathways including TLR4, NF-κB, and TNF. Secondly, an experimental study was carried out in vivo for verification. Our results demonstrated that YFBP could effectively improve the symptoms and intestinal pathological of UC rats. Further study showed that YFBP could significantly downregulate the expressions of TLR4 and p-NF-κB p65 in UC rats, inhibit the activation of NLRP3 inflammasome, reduce the levels of IL-1ß and TNF-α, and then upregulate the expressions of tight junction proteins in intestinal epithelial cells. In addition, YFBP could improve the intestinal microbial community. In conclusion, our study revealed that YFBP had a good therapeutic effect on UC, and its mechanism might be related to the inhibition of the TLR4/NF-κB/NLRP3 inflammasome signaling pathway to repair intestinal epithelial barrier and the modulation of intestinal microbiota.

Kappaphycus Alvarezii Compound Powder Prevents Chemotherapy-Induced Intestinal Mucositis in BALB/c Mice.

This study aimed to formulate Kappaphycus alvarezii compound powder containing Kappaphycus alvarezii powder (KP), cooked sorghum powder (SP), and longan powder (LP); which was evaluated for its therapeutic effects against chemotherapy-induced intestinal mucosal injury (CIMI). Based on rheological properties, sensory evaluation, and antioxidant activity and using single factor and response surface methodology, the optimal formula to develop the compound powder was determined to be 35% KP, 30% SP, 5% LP, and 30% xylitol. Thereafter, the efficacy of the compound powder was tested by feeding BALB/c mice with diets supplemented with the Kappaphycus alvarezii compound powder (3% and 5%) for 14 consecutive days. The chemotherapeutic drug 5-fluorouracil was intraperitoneally injected (50 mg/kg) in the mice to induce CIMI for the last three consecutive days. Compared to the CIMI mice, those fed 5% Kappaphycus alvarezii compound powder (HC) showed significantly improved the intestinal injury, increased mucin-2 secretion, and reduced TNF-α, IL-1ß, IL-6, LT, and COX-2 levels. Furthermore, HC intake significantly reduced the Firmicutes-to-Bacteroidetes ratio, promoted the growth of beneficial bacteria, such as Alloprevotella, and inhibited the growth of harmful bacteria, such as Clostridium. In conclusion, HC has a protective effect against CIMI and provides a novel dietary strategy for patients undergoing chemotherapy.

Effects of Qing Chang Suppository Powder and its Ingredients on IL-17 Signal Pathway in HT-29 Cells and DSS-induced Mice.

BACKGROUND: Qingchang Suppository, a formula used for more than 30 years in Longhua Hospital, has shown satisfactory clinical effects on Ulcerative Colitis (UC). However, its therapeutic mechanism has not been fully elucidated. PURPOSE: The study aims to investigate the effects of Qingchang Suppository powder (QCSP) and its ingredients by regulating the IL-17A signaling pathway which plays an important role in the development of UC. METHODS: HPLC was used to analyze the main ingredients (Gallic acid, Indigo, Indirubin) in QCSP. HT-29 cells were induced by rhIL-17A and TNF-α, and IL-17A related protein expressions were determined by western blot. BALB/C mice were induced by 4% Dextran Sodium sulfate (DSS). The effects of QCSP and its ingredients were evaluated by measuring weight loss, disease activity index (DAI), colon length, histological analysis. Western blot was used for analysis of IL-17A and MAPK related proteins p-ERK, p-JNK, p-P38. Quantitative reverse transcription polymerase chain reaction (q-PCR) was used to detect the expression of IL-17A, HSP90 and ACT1 in colon tissue. Cytokines such as IL-17A, IL-1ß, IFN-γ and TNF-α were determinated by enzyme-linked immunosorbent assay (ELISA). RESULTS: QCSP had good therapeutic effect on DSS-induced colitis in mice. QCSP significantly relieved weight loss, restored colon length, repaired colon lesions, reduced histological scores and DAI, decreased TNF-α, IL-1ß, IL-17 and IFN-γ contents, significantly suppressed the gene expressions of IL-17A, ACT1 and HSP90, and up-regulated the expressions of tight junction proteins like ZO-1 and Occludin. IL-17A pathway related proteins such as IL-17A, IL-17RA, HSP90, MAPKs, P-iκbα and iNOS were significantly increased in vitro and in vivo. CONCLUSIONS: This paper reveals that QCSP inhibited the IL-17A signaling pathway in HT-29 cells and DSS induced mice, presenting a new mechanism of QCS on treating UC.

Moringa oleifera leaf powder alters the pharmacokinetics of amodiaquine in healthy human volunteers.

WHAT IS KNOWN AND OBJECTIVE: Moringa oleifera (MO) Lam (Moringaceae) is commonly used as food supplement and as medicine in most African countries where malaria is also endemic. Therefore, co-administration of MO with antimalarials is a possibility. This study investigated the effects of MO leaves powder on the pharmacokinetics of amodiaquine (AQ) in human subjects. METHODS: Twenty healthy volunteers were recruited for the 3-period study. In the first period, a single dose of AQ tablet (10 mg/kg) was administered orally after an overnight fast. After a 7-day washout period, AQ was co-administered with MO. For the third period, each subject took 3 g MO once daily for 7 days and on the 8th day, MO was co-administered with AQ. The plasma concentrations of amodiaquine and desethylamodiaquine (DEAQ) were simultaneously determined using a validated HPLC method. RESULTS AND DISCUSSION: The results showed a significant decrease (P = .037) in the Cmax of AQ after concurrent administration (CA) with MO, whereas after pretreatment (PT), there was a 32% decrease in the Cmax of AQ. For the metabolite, DEAQ, Cmax increased significantly (P = .006) by 79.36%, and Cmax in PT was significantly higher than (P = .001) that of the CA arm of the study. AUC of DEAQ increased significantly by 40.4% (P = .006) and by 188% (P = .001) after CA and PT, respectively. WHAT IS NEW AND CONCLUSION: The study established pharmacokinetic interaction between AQ and MO when given together or following a long period of ingestion of MO. This may have clinical implications for malaria therapy.

Cardiovascular safety pharmacology studies in dogs enabled for a poorly soluble molecule using spray-dried dispersion: Impact on lead selection.

The aim of this study was to identify an adequate formulation for a poorly soluble lead molecule (BI-A) that would achieve sufficiently high plasma concentrations after oral administration in dogs to enable a robust cardiovascular safety pharmacology assessment in telemetry-instrumented conscious dogs during lead optimization in drug discovery. A spray-dried dispersion of BI-A (BI-A-SDD) containing a 1:2 ratio of BI-A and hydroxypropyl methylcellulose acetate succinate-LF was prepared using a Büchi spray dryer B-90 (B-90). Physical form characterization, an in vitro dissolution test and a preliminary pharmacokinetic (PK) study following oral administration of BI-A-SDD were performed. Thereafter, effects on cardiovascular parameters in conscious, chronically-instrumented dogs were investigated for 24h after a single oral dose (5, 10, and 50mg/kg) using a modified Latin square cross-over study design. The BI-A-SDD powder was confirmed to be amorphous and was stable as an aqueous suspension for at least 4h. The BI-A-SDD suspension provided a greater rate and extent of dissolution than the crystalline BI-A suspension and the supersaturation was maintained for at least 4h. In PK studies the Cmax of the BI-A-SDD formulation (25.4µM; 77-fold the projected efficacious Cmax of 0.33µM) was 7.5-fold higher than the Cmax observed using oral administration of a 10% hydroxypropyl-ß-cyclodextrin formulation at 100mg/kg in dogs (3.4µM). In conscious, chronically-instrumented dogs, the doses tested and plasma concentrations achieved were sufficient to enable a robust safety pharmacology evaluation. Multiple off-target hemodynamic effects were detected including acute elevations in aortic blood pressure (up to 22% elevation in systolic and diastolic blood pressure) and tachycardia (68% elevation in heart rate), results that were confirmed in other in vivo models. These results led to a deprioritization of BI-A. The study demonstrated that a spray-dried dispersion, prepared using the B-90 in drug discovery, enhanced the oral exposure of a poorly water-soluble molecule, BI-A, and thereby enabled its evaluation in safety pharmacology studies that ultimately resulted in deprioritization of BI-A from a pool of lead compounds.

Evaluation of Safety of Iron-Fortified Soybean Sprouts, a Potential Component of Functional Food, in Rat.

Ferritin-iron is currently considered as one of the most promising iron forms to prevent iron deficiency anaemia. We found that the cultivation of soybean seeds in a solution of ferrous sulfate results in material with extremely high iron content - 560.6 mg Fe/100 g of dry matter, while ferritin iron content was 420.5 mg/100 g dry matter. To assess the potential adverse effects of a preparation containing such a high concentration of iron, male and female Wistar rats were exposed via diet to 10, 30, 60 g soybean sprouts powder/kg feed for 90 days. There were no differences in final body weight and mean food consumption between controls and rats administered sprouts. No statistically significant differences in haematology and clinical chemistry parameters were found between controls and treated rats. Microscopic examination of 22 tissues did not reveal any pathology due to soybean sprouts intake. Long term administration of the test material did not cause oxidative damage to DNA and protein in the liver as evidenced by the unchanged basal levels of DNA damage as well as carbonyl groups content. Lipid peroxidation was slightly increased only in females. The activity of several antioxidant enzymes: superoxide dismutase, glutathione peroxidase and glutathione S-transferase was increased, which substantially enhanced the antioxidant status in the liver from the rats treated with soybean sprouts. Hence, the material tested can be recommended as a component of food supplements for individuals with iron deficiency anaemia and inflammatory bowel diseases.

Pharmacokinetics and safety of resveratrol derivatives in humans after oral administration of melinjo (Gnetum gnemon L.) seed extract powder.

Fruits and seeds of melinjo (Gnetum gnemon L.) are resveratrol derivative-rich materials. Pharmacokinetics of resveratrol derivatives in healthy volunteers after oral administration of 1000 mg of melinjo seed extract (MSE) powder were assessed and compared with those after oral dosing of trans-resveratrol (tRV) powder containing 4.8 mg of tRV only, equivalent to the content in 1000 mg MSE powder. Plasma tRV concentrations with enzymatic hydrolysis were maintained over 24 h, with a tmax of 12 h and a mean residence time (MRT) of 14 h, 5 and 2 times higher than those for tRV powder intake, respectively. Gnetin C, a resveratrol dimer, with hydrolysis was maintained in plasma for >96 h with a 36 h MRT. With repeated doses once daily for 28 days, plasma tRV and gnetin C concentrations with hydrolysis were in good agreement with the theoretical curves. MSE powder was well tolerated up to the oral dosing of 5000 mg with no serious adverse events.

Ocular powder: dry topical formulations of timolol are well tolerated in rabbits.

PURPOSE: Although eye drops are the most common form of ocular drugs, they have several limitations. Drug absorption into the eye is, in general, less than 5%, addition of preservatives is often necessary, and many drugs cannot be formulated as eye drops. Formulating ocular drugs as powder may solve these problems. The aim of this study was to investigate ocular irritation in rabbits following powder administration. METHODS: Timolol maleate (TM) powder was administered to pigmented lop rabbits. Both pure TM powder and freeze-dried with PVP-polymer (2.4% of mass) were tested in 1.0- and 0.1-mg doses. Additionally, 4 rabbits received 0.1 mg of the pure powder 3 times a day for 8 d. Redness of the bulbar conjunctiva and the amount of discharge was rated from photographs (0-3 points, randomized and masked evaluation). The 8-d experiment additionally included examination with a slit lamp and examination of hematoxylin-eosin stained sections of eyes with light microscopy. RESULTS: No serious or irreversible signs of irritation were noted. Doses of 1.0 mg were more irritating than 0.1-mg doses. There was no detectable difference in irritation between pure or freeze-dried powder. Slit-lamp examination, surface photographs and histology showed a negligible difference between drug and control eyes following the 8-d experiment. CONCLUSIONS: The results suggest that 0.1 mg of timolol powder does not irritate the eye and that testing topical timolol powder in humans is feasible.

In vivo hypolipidemic effects and safety of low dosage Monascus powder in a hamster model of hyperlipidemia.

Monascus or more commonly known as red mold rice is fermented rice on which Monascus purpureus has been grown. It has been a traditional Chinese food additive for thousands of years in China. Secondary metabolite product of Monascus, monacolin K, has been proven that it could be used as an antihypercholesterolemic agent. In this study, M. purpureus NTU568 mutated and selected from a monacolin K productivity strain-M. purpureus HM105 produced high quantities of monacolin K at a level of 9,500 mg kg(-1). This research focused on the effect of adding red mold rice powder of M. purpureus NTU568 to a hamster diet on total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol (LDL-C). In the results, the oral administration of Monascus powder in hyperlipidemia hamster was indeed proven to decrease TC, TG, and LDL-C levels. Plasma TC levels in hamster fed with Monascus powder at one-fold dosage [10.78 mg (day 100 g bw)(-1)] for 4 and 8 weeks were significantly lower (31.2 and 22.0%, respectively) than that in hyperlipidemia hamster. Plasma TG (30.1 and 17.9%) and LDL-C levels (36.0 and 20.7%) were also significantly lowered by feeding Monascus powder at one-fold dosage for 4 and 8 weeks compared to hyperlipidemia hamster. In addition, examinations of liver TC and TG levels of hyperlipidemia hamster were also performed and showed similar effects on lipid-lowering action by oral administration of Monascus powder. Since citrinin is a mycotoxin that possesses nephrotoxic and hepatoxic effects, it has a negative impact on the safety of red mold rice for people. This study examined the liver somatic index [plasma glutamyl oxaloacetic transaminase (GOT) and glutamyl pyruvic transaminase (GPT) levels] and liver biopsy to investigate whether Monascus powder induced damage in liver. It was found that the plasma GOT and GPT levels were not significantly increased by feeding Monascus powder. There was no difference in the results of the liver biopsy between the Monascus powder-treated groups and the control group.

Assessment of the activity of antiperspirants added to surgical hand disinfectants: methodological aspects and first observations.

Due to the risk of sensitization caused by glove powder, the use of unpowdered latex gloves is increasing. These unpowdered gloves need a special inner-surface layer which makes it easier for the applicant to put the glove on the hand and to remove it again. However, many users report difficulties with removing the gloves because of sweat production within the glove. Therefore, a method has been developed to evaluate the efficacy of antiperspirants which may be added either to the inner-surface layer of the glove or to hand disinfectants or to skin-care products used before the gloves are put on. The paper describes various trials to optimize this method.

Estudio de hipersensibilidad cutánea: intradérmica a extractos alergénicos y su relación con el lugar de residencia / Cotaneous hipersensitivity study: allergenic extracts intradermical and its relation with the living area

Revisión retrospectiva de 308 expedientes clínicos de pacientes que acuden al servicio de alergia e inmunología clínica del Centro Médico 20 de Noviembre del ISSSTE por cursar con padecimientos alérgicos, realizada para determinar la frecuencia de sensibilización a aeroalergenos (mediante intradermorreacciones) y su relación con la zona en que habitaban. Los pacientes fueron más sensibles al polvo y dermatofagoides (75 y 40 por ciento respectivamente). Otros aeroalergenos que causaron sensibilización en los pacientes fueron Capriola dactylon (37.6 por ciento), Amaranthus palmieri (35.5 por ciento), fracxinus (34.6 por ciento), Ambrosia elatior (33 por ciento), Cándida (21.4 por ciento), penicillium (18.1 por ciento), Mucor y Rizipus (17.8 por ciento cada uno).

Asthma from psyllium in laxative manufacture.

Symptoms of asthma developed in three patients after exposure to psyllium powder, which was being used in the manufacture of a bulk laxative. All three had reaginic skin test sensitivity, and two had positive bronchial challenges with a psyllium extract.